1. Field of the Invention
This invention relates generally to new polypeptides, to methods for preparation of the new polypeptides, and fields of use for the polypeptides.
2. Description of the Prior Art
It is well known that many polypeptides have been isolated from various organs of animals. Until about the past decade, however very little was known about the thymus, an organ which in man comprises about 0.8% of his body weight at birth, although it has been previously hypothesized that a neuromuscular blocking substance existed in the thymus. Despite keen interest in possible functions of the thymus and early speculation and experimentation, little was known of the function of the thymus until recently. It is now realized, however, that the thymus is a compound organ with both epithelial (endocrine) and lymphoid (immunological) compounds and thus the thymus is involved in the immunity functions of the body. The thymus is known to be a compound organ consisting of an epithelial stroma derived from the third branchial arch and lymphocytes derived from stem cells originating in haemopoietic tissues, Goldstein et al, The Human Thymus, Heinemann, London, 1969. Lymphocytes are differentiated within the thymus and leave as mature thymus-derived cells, called T cells, which circulate to the blood, lymph, spleen and lymph nodes. The induction of stem cell differentiation within the thymus appears to be mediated by secretions of the epithelial cells of the thymus but difficulties with bioassays had previously hindered the complete isolation and structural characterization of any hormones which may be present.
It has been known for some time that the thymus is connected with the immunity characteristics of the body and therefore great interest has been indicated in substances which have been isolated from the thymus. In this regard, there have been published in recent years a relatively large body of articles based on scientific work relating to materials which are present in bovine thymus. In fact, the Applicants have published a number of articles which relate to research in this area. Pertinent publications may be found for example in The Lancet, July 20, 1968, pps. 119-122; Triangle, Vol. 11, No. 1, pps. 7-14, 1972; Annals of the New York Academy of Sciences, Vol. 183, pps. 230-240, 1971; and Clinical and Experimental Immunology, Vol. 4, No. 2, pps. 181-189, 1969; Nature, Vol. 247, pps. 11-14, 1974; Proceedings of the National Academy of Sciences USA, Vol. 71, pps. 1474-1478, 1974; Cell, Vol. 5, pps 361-365 and 367-370, 1975; Lancet, Vol. 2, pps. 256-259, 1975; Proceedings of the National Academy of Sciences USA, Vol. 72, pps. 11-15, 1975; Biochemistry, Vol. 14, pps 2214-2218, 1974; Nature, Vol. 255, pps. 423-424, 1975.
In the article by Goldstein and Manganaro in Annals of the New York Academy of Sciences, Vol. 183, pps. 230-240, 1971, there are disclosures regarding the presence of a thymic polypeptide which causes a myasthenic neuromuscular block in animals, which is analogous to the human disease of myasthenia gravis. Further, in this article it was discovered that two distinct effects were caused by separate polypeptides in bovine thymus. One of these polypeptides, named "thymotoxin," was believed to cause myositis but it was further indicated that this polypeptide of approximately 7,000 molecular weight, had a strong net positive charge and was retained on CM-Sephadex at a pH of 8.0.
In the publication "Nature," 247, 11, Jan. 4, 1975, there are described products identified as Thymin I and Thymin II which were found to be new polypeptides isolated from bovine thymus which have particular uses in various therapeutic areas. Because of the use of similar names for other products isolated from the thymus in the prior art, these Thymin I and Thymin II products are now named as Thymopoietin I and Thymopoietin II. These products and processes are described in U.S. Pat. No. 4,077,949, issued Mar. 7, 1978, from application Ser. No. 606,843, filed Aug. 22, 1975, which is a continuation-in-part of application Ser. No. 429,202, filed Dec. 28, 1973, and now abandoned.
In issued U.S. Pat. No. 4,002,602, dated Jan. 11, 1977, which is a continuation-in-part of application Ser. No. 449,686, filed Mar. 11, 1974, and now abandoned, there are disclosed long chain polypeptides described as Ubiquitous Immunopoietic Polypeptide (UBIP). This peptide has subsequently been renamed as Ubiquitin. This polypeptide is a 74-amino acid polypeptide characterized by its ability to induce in vitro, in nanogram concentrations, the differentiation of both T-cell and B-cell immunocytes from precursors present in bone marrow or spleen. Thus, the polypeptide is useful in therapeutic areas involving thymic or immunity deficiencies and the like.
In issued U.S. Pat. No. 4,002,740, dated Jan. 11, 1977, there are disclosed synthesized tridecapeptide compositions which have the capability of inducing the differentiation of T-lymphocytes but not of complement receptor B-lymphocytes. This polypeptide thus exhibited many of the characteristics of the long chain polypeptides isolated and named as thymopoietin in above-mentioned U.S. Pat. No. 4,077,949.
The present invention provides a synthesized five-amino acid polypeptide having a definite active site sequence which has been found to exhibit many of the characteristics of the long chain polypeptide isolated and named as Ubiquitous Immunopoietic Polypeptide (UBIP) in the above publications and U.S. Pat. No. 4,002,602, dated Jan. 11, 1977.